Associations Between TIM1 Polymorphisms and Dilated Cardiomyopathy in a Han Chinese Population

Abstract

Immune dysfunction is implicated in dilated cardiomyopathy (DCM). Previous studies found that TIM1 polymorphisms were associated with immune dysfunction. However, the associations between TIM1 polymorphisms and DCM have not been investigated. Therefore, we conducted the present study to evaluate whether TIM1 polymorphisms were associated with DCM in the Han Chinese population. A total of 396 DCM patients and 403 healthy controls were enrolled in this case-control study. Two promoter region single nucleotide polymorphisms (SNPs) of TIM1 gene, -416G>C and -1454G>A, were genotyped by PCR-RFLP. The associations between two SNPs genotyped and the overall survival (OS) of DCM patients were evaluated with Kaplan-Meier analysis and Cox regression analysis. Plasma TIM-1 levels were further measured by ELISA. We found that the C allelic frequency of -416G>C and A allelic frequency of -1454G>A were higher in DCM patients than that in controls (P < 0.001). The genotypic frequencies of both SNPs were associated with DCM susceptibility in the codominant, dominant, and overdominant models (P < 0.01). They were also associated with the OS of DCM patients in the dominant, recessive, and overdominant models (P < 0.001). The CC genotype of -416G>C and AA genotype of -1454G>A were associated with the worst prognosis (P < 0.001). In addition, the plasma TIM-1 levels in DCM patients were higher than that in controls (259.0 pg/mL versus 149.8 pg/mL, P = 0.035). The CC genotype of 416G>C and AA genotype of -1454G>A were associated with the highest TIM-1 production (P < 0.01). Overall, our findings suggest that TIM1 polymorphisms are associated with DCM susceptibility and prognosis in this Han Chinese population.